Impact of COVID-19 Pandemic on Global Unrelated Stem Cell Donations in 2020 - Report from World Marrow Donor Association

Abstract Introduction: World Marrow Donor Association (WMDA) promotes global collaboration for the benefit of stem cell donors and transplant patients. WMDA activities include recording the number of unrelated hematopoietic stem cell (HSC) donations globally. Because the COVID-19 pandemic also has an impact on the treatment of patients with other diseases, we hypothesise that it also impacted the practice of unrelated hematopoietic stem cell transplantation (HSCT). We used the 2020 WMDA data to examine the trends in unrelated HSC donations during the COVID-19 pandemic globally, per continent and per country/region. Methods: Donor registries (DRs) and cord blood banks (CBBs) from 61 countries participated in the 2020 survey, compared to 59 countries in the 2019. Slight differences in participation between the data sets of 2019 and 2020 do not explain the trends we observe in HSC donations. Country/region-specific COVID-19 data on cases and deaths were obtained from the data repository operated by the Johns Hopkins University Center for Systems Science and Engineering(https://github.com/CSSEGISandData/COVID-19, accessed July 12, 2021); and population data were retrieved from the Worldometer website(https://www.worldometers.info/, accessed July 12, 2021). Results: HSC donations from unrelated donors (peripheral blood stem cells (PBSC) and bone marrow (BM)) decreased from 20,330 in 2019 to 19,623 in 2020 (-3.5%), compared to an average annual growth rate of 3.9% from 2015 to 2019 (figure 1). The 3.5% decrease is composed of a 29.0% decrease for BM and a 2.6% increase for PBSC, resulting in a drop in the BM share of unrelated HSC donations from 19.3% in 2019 to 14.2% in 2020. The number of cord blood unit (CBU) shipments globally decreased with 3.5% from 2,851 to 2,750. The percentage of national use of HSC products (PBSC and BM) increased from 51.2% to 53.5%. When considering the continent on which the patient is transplanted (table 1), the change rate of use of HSC donated products in 2020 vs. 2019 ranged from -28.0% in South America to +18.2% in Africa. In absolute numbers, the largest decrease of HSC donations occurred for patients in Asia (n=-485) followed by Europe (n=-205), and the largest increase occurred in North America (n=+88) followed by Oceania (n=+25). The share of HSC donations requiring intercontinental transport decreased from 24.6% in 2019 to 21.9% in 2020. In terms of the country/region of transplant (table 2), the largest percentage decrease occurred in Colombia (-90,5%) followed by Russia (-55,5%). In absolute numbers, the largest decrease occurred in Turkey (-147), with Japan following (-128, although Japan saw an increase of CBU use of +106). The highest growth rate was observed in Iran (+28,7%), followed by South Africa (+28,2%). In absolute figures, the greatest increase occurred in Italy (+67). The two countries receiving the largest HSC donation numbers showed no major changes versus the previous year: USA: +0.6% (although a decrease for CBU of -21,0% was observed) and Germany: -2.4%. We did not find any significant correlation between the numbers of COVID-19 cases or COVID-19-related deaths per 1 million inhabitants with the HSC donation numbers (Spearman's r=0.05 for cases and =0.08 for deaths). Discussion: The decline in the number of unrelated HSC donations in 2020 suggests an impact of the COVID-19 pandemic on HSC donation and unrelated HSCT. The significant decrease in BM collections and intercontinental/cross-border shipments can be explained by logistically complex processes, as well the increased risk to the donor of being exposed to an operative procedure. CBU as a stem cell source potentially circumvents these logistical complications. However, on a global scale our data does not show increased use of CBU suggesting that decisions to use CBU as a stem cell source did not change in the pandemic . We were unable to demonstrate a correlation between country/region-specific severity of the pandemic and HSC donation numbers. We suspect this is due to the data quality of reported number of COVID-19 cases and COVID-19-related deaths. Also, we did not gather monthly data and therefore could not specify pandemic waves. In conclusion, we would like to point out the fact that global exchanges of HSC products continued and only decreased slightly is an extraordinary achievement of DRs, CBBs and their donors and is a testament to the importance of international collaborations in the WMDA. Figure 1 Figure 1. Disclosures Devine: Orca Bio: Consultancy, Research Funding; Johnsonand Johnson: Consultancy, Research Funding; Sanofi: Consultancy, Research Funding; Magenta Therapeutics: Current Employment, Research Funding; Tmunity: Current Employment, Research Funding; Vor Bio: Research Funding; Kiadis: Consultancy, Research Funding; Be the Match: Current Employment. Shaw: Orca bio: Consultancy; mallinkrodt: Other: payments. Forman: Mustang Bio: Consultancy, Current holder of individual stocks in a privately-held company; Lixte Biotechnology: Consultancy, Current holder of individual stocks in a privately-held company; Allogene: Consultancy.

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A consideration for efficient unrelated hematopoietic stem cell source acquisition—from an experience of Japan

Bone Marrow Transplantation ◽

10.1038/s41409-019-0542-0 ◽

2019 ◽

Vol 55 (3) ◽

pp. 657-660

Author(s):

Satoshi Nishiwaki ◽

Koichi Miyamura ◽

Yoshinobu Kanda ◽

Minoko Takanashi ◽

Naoyuki Uchida ◽

...

Keyword(s):

Stem Cell ◽

Hematopoietic Stem Cell ◽

Hematopoietic Stem ◽

Stem Cell Source ◽

Cell Source

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What Is the Most Appropriate Source for Hematopoietic Stem Cell Transplantation? Peripheral Stem Cell/Bone Marrow/Cord Blood

Bone Marrow Research ◽

10.1155/2012/834040 ◽

2012 ◽

Vol 2012 ◽

pp. 1-5 ◽

Cited By ~ 11

Author(s):

Itır Sirinoglu Demiriz ◽

Emre Tekgunduz ◽

Fevzi Altuntas

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Cord Blood ◽

Cell Transplantation ◽

Hematopoietic Stem ◽

Stem Cell Source ◽

Cell Source ◽

Selection Of

The introduction of peripheral stem cell (PSC) and cord blood (CB) as an alternative to bone marrow (BM) recently has caused important changes on hematopoietic stem cell transplantation (HSCT) practice. According to the CIBMTR data, there has been a significant decrease in the use of bone marrow and increase in the use of PSC and CB as the stem cell source for HSCT performed during 1997–2006 period for patients under the age of 20. On the other hand, the stem cell source in 70% of the HSCT procedures performed for patients over the age of 20 was PSC and the second most preferred stem cell source was bone marrow. CB usage is very limited for the adult population. Primary disease, stage, age, time and urgency of transplantation, HLA match between the patient and the donor, stem cell quantity, and the experience of the transplantation center are some of the associated factors for the selection of the appropriate stem cell source. Unfortunately, there is no prospective randomized study aimed to facilitate the selection of the correct source between CB, PSC, and BM. In this paper, we would like to emphasize the data on stem cell selection in light of the current knowledge for patient populations according to their age and primary disease.

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Early Immune Reconstitution after Hematopoietic Stem Cell Transplantation for Adolescents and Adults with Sickle Cell Disease

Blood ◽

10.1182/blood-2021-147133 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 3907-3907

Author(s):

Loïc Vasseur ◽

Florence Morin ◽

Corinne Pondarré ◽

Florian Chevillon ◽

Aude-Marie Fourmont ◽

...

Keyword(s):

Stem Cell ◽

Research Funding ◽

Immune Reconstitution ◽

Normal Values ◽

Advisory Committees ◽

Hematopoietic Stem ◽

Post Transplant ◽

Stem Cell Source ◽

Cell Source ◽

Adolescents And Adults

Abstract Introduction Allogeneic hematopoïetic stem cell transplantation (HSCT) is the only established curative therapy for patients (pts) with sickle cell disease (SCD). It is mostly performed in children 1, due to higher risk of graft-versus-host disease (GVHD) and transplant related mortality in adults. Different approaches have been developped to improve tolerance of transplant in adults: use of reduced intensity conditioning (RIC) regimens 2 and intensive immunosuppression to avoid GVHD. Here, we have studied the impact of such approaches on immune reconstitution in adolescents and adults transplanted for SCD. Patients and methods We report 39 transplants in adolescents and adults, performed in Saint Louis hospital from 2008 to 2020: 25 were matched related transplants (MRT) and 14 haplo-identical related transplant (HRT). In MRT, conditioning was myeloablative (MAC) in 15 pts (busulfan, cyclophosphamide, rabbit anti-thymoglobulin (ATG) 20 mg/kg) and non myeloablative (NMA) in 10 pts (alemtuzumab 1 mg/kg, 3 Gy total body irradiation (TBI)). In MAC transplants, stem cell source was bone marrow and post-transplant immunosuppression was methotrexate and cyclosporine. In NMA transplants, stem cell source was peripheral blood cells with post-transplant immunosuppression by sirolimus. In the 14 HRT, the conditioning was reduced (cyclophosphamide, thiotepa, fludarabine, 2 Gy TBI, ATG 4.5 mg/kg), stem cell source was bone marrow and GVHD prophylaxis was ensured by post-transplant cyclophosphamide (100 mg/kg), sirolimus and mycophenolate mofetil. Results Median age at transplant was 17 years (y) old (range (r) 14-39). With a median follow-up of 3.6 y, the 2-y overall survival and survival without SCD were 97% (IC95%: 0.92-1) and 92% (IC95%: 0.83-1) respectively: no event after MRT, 1 death of GVHD and 2 graft rejections after HRT. The acute GVHD grade II-IV rate was 33%: 21% after HRT, 13% after MAC MRT and 0% after NMA MRT. Chronic GVHD occured in 3 pts (8%): severe in 1 HRT and mild in 2 MAC MRT. At 6 months, the blood chimerism evaluated in the 36 patients alive without rejection, was more often mixed (5 to 95% of donor) after NMA MRT (100%) versus MAC MRT (40%, p = 0.003) and HRT (18%, p < 0.001). Total lymphocytes (TL) counts increased rapidly in HRT and MAC MRT with a normalization from 3 months post-transplant. In contrast, NMA MRT experienced a slower recovery: at 6 months, median count was 1039/mm3 (r 463-1767) compared to 2071/mm3 (r 882-5985, p = 0.002) after MAC MRT and 2382/mm3 (r 676-3978, p = 0.005) after HRT. After NMA MRT, TL counts remained lower than normal values up to 12 months with a median of 1195/mm3 (r 870-3210) (Figure 1A). HRT displayed a rapid normalization of CD4 counts with a 3-month median count of 645/mm3 (r 350-1076) higher than reported after MRT (p < 0.001). Evolution of CD4 counts was similar after NMA and MAC MRT. They were lower than normal values during the first 12 months: median 364/mm3 and 388/mm3 respectively at 12 months (p = 0.25) (Figure 1B). From 3 months post-transplant, CD8 counts reached normal values after MAC MRT (314/mm3, r 108-2175) and were superior to normal after HRT (1335/mm3, r 66-4529), with a significant difference between HRT and MRT (p = 0.003). After NMA MRT, there was a trend for lower 3-month CD8 counts compared to MAC MRT: median of 107/mm3 (r 18-631, p = 0.08). CD8 counts remained under normal values after NMA MRT up to 12 months post-transplant (Figure 1C). From 3 to 6 months, CD4 and CD8 were mostly memory, with only 3.2% (r 0.1%-20.6%) and 6.2% (r 2.1%-11.2%) of CD45RA+ CCR7+ naïve CD8+ and CD4+ respectively. In the 3 groups NK cell counts reached normal values after 3 months. B lymphocytes counts normalized in the first months post-transplant except for patients who received rituximab for EBV reactivation. From 3 to 6 months, B lymphocytes were mostly naive: 98% of CD27- (r 92%-99%). Gammaglobuline levels were normal from 3 months in the 3 groups. Twelve (31%) pts were treated for a CMV and 6 (15%) for an EBV reactivation. No patient had CMV or adenovirus disease, or post-transplant lymphoproliferative disorder. Infections according to transplant types are detailed in figure 1D. Conclusion NMA MRT were associated with a delayed CD4 and CD8 recovery probably due to alemtuzumab. As previously reported 3, HRT displayed a rapid immune reconstitution. Despite use of serotherapy in the three modalities of transplant, the rate of viral infections remained acceptable without severe episode. Figure 1 Figure 1. Disclosures Pondarré: ADDMEDICA: Honoraria. Peffault De Latour: Jazz Pharmaceuticals: Honoraria; Pfizer: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Amgen: Consultancy, Other, Research Funding; Alexion, AstraZeneca Rare Disease: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding. Boissel: CELGENE: Honoraria; Bristol-Myers Squibb: Honoraria, Research Funding; JAZZ Pharma: Honoraria, Research Funding; Incyte: Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Servier: Consultancy, Honoraria; SANOFI: Honoraria; PFIZER: Consultancy, Honoraria.

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Haploidentical Hematopoietic Stem Cell Transplantation In Hematologic Malignancies with G-CSF Mobilized Bone Marrow Plus Peripheral Blood Stem Cells Grafts without T Cell Depletion: a Single Center Report of 29 Cases

Blood ◽

10.1182/blood.v116.21.3552.3552 ◽

2010 ◽

Vol 116 (21) ◽

pp. 3552-3552

Author(s):

Hengxiang Wang ◽

Hongmin Yan ◽

Zhidong Wang ◽

Mei Xue ◽

Ling Zhu ◽

...

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

Hematopoietic Stem Cell ◽

Peripheral Blood ◽

Peripheral Blood Stem Cell ◽

Blood Stem Cell ◽

Hematopoietic Stem ◽

Platelet Recovery ◽

Stem Cell Source ◽

Cell Source

Abstract Abstract 3552 Introduction: Haploidentical Hematopoietic stem cell transplantation (Haplo-HSCT) has provided an alternative option since virtually all patients have an immediately available donor. In order to reduce the occurrence of severe acute GVHD, initially we used donor bone marrow with G-CSF mobilization as hematopoietic stem cell source and achieved good effect. However, as this work carried out widely, it is difficult to collect enough bone marrow cells from donor due to the much differences body weight between the recipient and donor, and lead to patients with hematopoietic recovery slowly. From February 2003 we started trying to use bone marrow and peripheral blood stem cell as stem cell source. Patients and Methods: Twenty-nine patients with hematologic malignancies were enrolled in this study between February 2003 and August 2007 at the general hospital of air force. Conditioning regimen consisting of high-doses of cytarabine and cyclophosphamide with total body irradiation, while 6 cases were preconditioned with busulfan, cytarabine and cyclophosphamide. aGVHD was prevented by a combination of immunosuppressive drugs including a monoclonal antibody against human CD25 (basiliximab), cyclosporine A (CsA), methotrexate (MTX), mycophenolate mofetil (MMF), and a rabbit anti-thymocyte globulin. Donors were given G-CSF at a dose of 300μg daily for 6 consecutive days prior to marrow harvesting. Peripheral blood stem cell was collected on the 7th day. Results: All patients attained successful neutrophil and platelet recovery. The median time to neutrophil engraftment was 17.1days, and that of platelet recovery was 20.9 days. The incidence of grade II-‡W GVHD was 31.03% and grade III-‡W GVHD was 13.79%. The GVHD-related death was 3.45%. The incidence of cGVHD was 48.2%. The incidence of extensive cGVHD was 23.3%. The incidence of diseases relapsed was 13.79%. A median follow-up of 54 months noted that 13 patients died, while 16 survived. The total disease-free survival rate longer than 3 years was 55%. Conclusion: G-CSF mobilization bone marrow and peripheral blood stem cell as stem cell source for Haplo-HSCT provided rapid and sustained engraftment without increase of severity GVHD. The rate of disease relapse was reduced. This treatment was particularly suitable for patients with heavier weight. Disclosures: No relevant conflicts of interest to declare.

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Infectious disease complications after unrelated donor hematopoietic stem cell transplantation in children: Impact of stem cell source

Biology of Blood and Marrow Transplantation ◽

10.1016/j.bbmt.2004.06.027 ◽

2004 ◽

Vol 10 (10) ◽

pp. 737-738

Author(s):

J. Barker ◽

J.E. Wagner

Keyword(s):

Infectious Disease ◽

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Hematopoietic Stem Cell ◽

Unrelated Donor ◽

Hematopoietic Stem ◽

Stem Cell Source ◽

Cell Source

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Influence of the hematopoietic stem cell source on early immunohematologic reconstitution after allogeneic transplantation

Blood ◽

10.1182/blood.v97.9.2580 ◽

2001 ◽

Vol 97 (9) ◽

pp. 2580-2586 ◽

Cited By ~ 27

Author(s):

Valérie Lapierre ◽

Nadia Oubouzar ◽

Anne Aupérin ◽

Dominique Tramalloni ◽

Hakim Tayebi ◽

...

Keyword(s):

Stem Cell ◽

Hematopoietic Stem Cell ◽

Conditioning Regimen ◽

Allogeneic Transplantation ◽

Phase Iii ◽

Hematopoietic Stem ◽

Stem Cell Source ◽

Cell Source ◽

A Minor ◽

Stimulating Factor

Abstract Several acute hemolysis episodes, sometimes lethal, have been recently described after transplantation of allogeneic peripheral blood hematopoietic stem cells (PBHSCs). Hemolysis resulted from the production of donor-derived antibodies (Abs) directed at ABO antigens (Ags) present on recipient red blood cells (RBCs). A multicenter randomized phase III clinical study comparing allogeneic PBHSC transplantation (PBHSCT) versus bone marrow hematopoietic stem cell transplantation (BMHSCT) has been conducted in France. In the course of this study, serum anti-A and/or anti-B Ab titers were compared before the conditioning regimen and on day +30 after transplantation in 49 consecutive evaluable PBHSCT (n = 21) or BMHSCT (n = 28) recipients. PBHSCT resulted in a higher frequency of increased anti-A and/or anti-B Ab titers 30 days after transplantation as compared to BMHSCT: 8 (38%) of 21 versus 3 (11%) of 28 (P = .04). In PBHSCT recipients, increased titers were observed mostly after receiving a minor ABO mismatch transplant: 5 of 7 versus 3 of 14 in the absence of any minor ABO mismatch (P = .05), whereas this was not the case after BMHSCT: 1 of 8 versus 2 of 20. Anti-A and/or anti-B serum Abs detectable at day +30 after PBHSCT were always directed against A and/or B Ags absent both on donor and recipient RBCs. Finally, 3 of 21 PBHSCT versus 0 of 28 BMHSCT recipients developed anti-allogeneic RBC Abs other than ABO (P = .07). Overall, the data strongly suggest that immunohematologic reconstitution differs significantly after granulocyte colony-stimulating factor–mobilized PBHSCT when compared to BMHSCT. Such a difference could contribute to the acute hemolysis described after PBHSCT as well as to distinct alloreactivity after PBHSCT.

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